Neuromyelitis Optica

NORD gratefully acknowledges Brian Weinshenker, MD, FRCP(C), Professor of Neurology, Mayo Clinic, for assistance in the preparation of this report.

Synonyms of Neuromyelitis Optica

(Asian, Japanese) opticospinal MS

Devic disease

Devic syndrome

optic neuromyelitis

opticomyelitis

Subdivisions of Neuromyelitis Optica

monophasic neuromyelitis optica

neuromyelitis optica spectrum disorders

relapsing neuromyelitis optica

General Discussion

Neuromyelitis optica, also known as Devic disease (DD), is a chronic disorder of nerve tissue characterized by inflammation of the optic nerve (optic neuritis) and inflammation of the spinal cord (myelitis). There appear to be two forms of this disease. In the classical, but less common monophasic type, one or both optic nerves and the spinal cord are affected by a series of attacks over a short period of time (days or weeks) but, after the initial outburst, there is no recurrence. The second form is more common and is characterized by repeated attacks separated by periods of remission. In this form, the interval between attacks may be weeks, months or years. In its early stages, Devic disease may be confused with multiple sclerosis.

Signs & Symptoms

The characteristic symptoms of neuromyelitis optica are either optic neuritis or myelitis; either may occur as the first symptom. Optic neuritis is inflammation, of the optic nerve (optic neuritis) leading to pain inside the eye which rapidly is followed by loss of clear vision (acuity). Usually, only one eye is affected (unilateral) although both eyes may be involved simultaneously (bilateral). Neuromyelitis optica may or may not be preceded by a prodromal upper respiratory infection.

The other cardinal syndrome is inflammation of the spinal cord, a condition known as transverse myelitis because the symptoms tend to affect all motor, sensory and autonomic functions (bladder and bowel) below a certain level on the body. Affected individuals may experience pain in the spine or limbs, and mild to severe paralysis (paraparesis to paraplegia) of the lower limbs, and loss of bowel and bladder control. Deep tendon reflexes may be diminished or absent initially and later become exaggerated. A variable degree of sensory loss may occur. Affected individuals may also have a stiff neck, back or limb pain, and/or headaches. This syndrome may be indistinguishable from other cases of “idiopathic” transverse myelitis.

Early in the course of the disease, it may be difficult to distinguish between neuromyelitis optica and multiple sclerosis because both may cause optic neuritis and myelitis as symptoms. However, the optic neuritis and myelitis tend to be more severe in neuromyelitis optica; the brain MRI is more commonly normal, and the spinal fluid analysis does not usually show oligoclonal bands in neuromyelitis optica, which are features that help distinguish it from MS.

In most cases of neuromyelitis optica, the initial symptoms of vision loss or paralysis improve with standard treatment with high dose corticosteroids, and partial recovery of vision, motor, sensory, or bladder function occurs. However, in recurring cases, neuromyelitis optica frequently causes significant permanent disturbances of vision and/or spinal cord function leading to blindness or impaired mobility.

Some patients with neuromyelitis optica have only recurrent myelitis or only recurrent optic neuritis. When patients have antibodies to aquaporin-4 with just these manifestations, most investigators would argue that they should be treated as having neuromyelitis optica. Brain lesions may occur in patients with neuromyelitis optica, typically, but not always, in later phases of the disease. Intractable vomiting or hiccups is now a generally accepted specific syndrome of this condition and is the result of inflammation in the dorsal medulla of the brainstem and may be the initial symptom of neuromyelitis optica. Brainstem and hypothalamic syndromes are particularly common, but inflammation of the forebrain may also occur, often associated with prominent brain swelling (edema). Clinicians suspecting this disorder must have a strong index of suspicion for this condition especially in patients with a history of severe myelitis or optic neuritis.

Neuromyelitis optica can also be associated with systemic autoimmune disease.

Causes

Greater than 95% of patients with neuromyelitis optica report no relatives with the disease, but approximately 3% report having other relatives with the condition. There is a strong association with a personal or family history of autoimmunity, which are present in 50% of cases. Neuromyelitis optica is regarded as an autoimmune disease though the exact cause for the autoimmunity is unknown.

Autoimmune disorders occur when the body’s natural defenses against disease or invading organisms (such as bacteria), for unknown reasons, suddenly begin to attack healthy tissue. These defenses, for reasons not at all understood, attack proteins in the central nervous system, especially aquaporin-4. In some patients with neuromyelitis optica, especially those with the non-relapsing variant, antibodies to myelin oligodendrocyte glycoprotein have been discovered by investigators in the U.K. and Japan which may be associated with this disorder. Neuromyelitis optica may be immunologically heterogeneous.

Affected Populations

Neuromyelitis optica occurs in individuals of all races. The prevalence of neuromyelitis optica is approximately 1-5 per 100,000 individuals and seems to be similar worldwide. Relative to MS that it mimics, it occurs with greater frequency in individuals of Asian descent and possibly in individuals of African descent, but the majority of patients with this illness in Western countries are Caucasian. Individuals of any age may be affected, but typically neuromyelitis optica occurs in late middle-aged women. Equal numbers of men and women have the form that does not recur after the initial flurry of attacks, but women are four or five times more likely to be affected than men by the recurring (relapsing) form. Children represent may also be affected by this condition; children more commonly develop brain symptoms at onset and seem to have a higher frequency of monophasic presentation.

Related Disorders

Symptoms of the following disorders can be similar to those of neuromyelitis optica. Comparisons may be useful for a differential diagnosis:

Acute disseminated encephalomyelitis (postinfectious encephalitis) is a central nervous system disorder characterized by inflammation of the brain and spinal cord caused by damage to the fatty sheath surrounding the nerves. This can occur spontaneously, but usually follows a viral infection or inoculation such as a bacterial or viral vaccine.

Multiple sclerosis is a chronic disease of the brain and spinal cord (central nervous system) which may be progressive, relapsing and remitting, or stable. The pathology of MS consists of small lesions called plaques that form randomly throughout the brain and spinal cord. In these plaques, the fatty sheath surrounding nerves is lost, which prevents proper transmission of nervous system signals and thus result in a variety of neurological symptoms. Most individuals with MS have a near normal life span. Symptoms often include visual difficulties as well as speech impairment, abnormal skin sensations or numbness, gait disturbance, and difficulties with bladder and bowel function. In a small number of cases, selective involvement of the optic nerves and spinal cord may occur in early stages of MS, but in these situations rarely would the spinal cord information extend over long segments of the spinal cord as occurs in neuromyelitis optica. (For more information on this disorder, choose “Multiple Sclerosis” as your search term in the Rare Disease Database.)

Systemic lupus erythematosus (also known as lupus) is an inflammatory connective tissue disease that can affect many parts of the body including the joints, skin and internal organs. Lupus is a disease of the body’s immune system, most often striking young women between the ages of fifteen and thirty-five years. (For more information on this disorder, choose “Lupus” as your search term in the Rare Disease Database.) Transverse myelitis and optic neuritis have been reported to occur in patients with systemic lupus erythematosus, but recent research demonstrates that a high proportion of such individuals have the NMO-IgG antibody, and likely have coexisting neuromyelitis optica.

Paraneoplastic disorders are conditions in which patients develop inflammation or cell injury caused by autoimmune reactions to a cancer that leads to production of autoantibodies or cell-mediated autoimmunity. In some paraneoplastic syndromes, particularly those associated with collapsin response mediated protein 5 (CRMP5), optic neuritis and extensive myelitis may occur that may closely simulate neuromyelitis optica.

Sarcoidosis is a granulomatous disorder that may affect the optic nerves and spinal cord when it affects the central nervous system. This condition frequently presents with pulmonary disease, either symptomatic or asymptomatic, or enlarged lymph nodes, often present on chest xray. Many patients with central nervous system involvement do not have demonstrable sarcoidosis in other organs. Sarcoidosis may result in long inflammatory spinal cord lesions that mimic the myelitis in neuromyelitis optica, but symptoms usually develop more insidiously and regress more slowly following corticosteroid treatment.

Diagnosis

A diagnosis of neuromyelitis optica is made based upon a detailed patient history, a thorough clinical evaluation, identification of characteristic physical findings, and a variety of specialized tests. Such tests include blood tests, examination of cerebrospinal fluid (CSF), spinal taps, or x-ray procedures such as magnetic resonance imaging (MRIs) or computed tomography (CT or CAT) scans. A blood test, NMO-IgG, is highly specific and moderately sensitive for neuromyelitis optica. It has been shown that it detects antibodies that are specific for an astrocyte protein, aquaporin-4. This is very helpful to request this test at the first significant suspicion of neuromyelitis optica, as it is frequently positive at the time of the very first symptom even before a confident clinical diagnosis is possible. Successful diagnosis of neuromyelitis optica depends on distinguishing it from MS.

Standard Therapies

Treatment
For acute attacks, the standard treatment is high-dose intravenous corticosteroids, typically methylprednisolone. Plasma exchange may be effective in patients who experience acute severe attacks that do not response to intravenous corticosteroids. This procedure involves removing some blood and mechanically separating the blood cells from the fluid (plasma). Blood cells are then mixed with a replacement solution and returned to the body.

For long-term suppression of the disease, no specific treatment has been studied in controlled clinical trials, but a variety of immunosuppressive drugs are regarded by many clinicians as first-line therapy. Corticosteroids, azathioprine, mycophenolate mofetil and rituximab are the treatments most widely prescribed treatments. Typically, azathioprine or mycophenolate mofetil are prescribed along with low doses of corticosteroids. Rituximab has been shown to be helpful in retrospective studies, including in patients who fail first-line immunosuppressive treatments. Immunomodulatory drugs for multiple sclerosis are ineffective, and in the case of interferon beta, there is some evidence that suggest that they may be harmful.

Symptom treatment may also involve the use of low doses of carbamazepine to control paroxysmal (sudden) tonic spasms that often occur during attacks of neuromyelitis optica and antispasticity agents to treat long term complication of spasticity that frequently develops in those with permanent motor deficits.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:www.centerwatch.com

Years Published

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